What is the approach to correcting elevated International Normalized Ratio (INR) with vitamin K in patients with cirrhosis?

From the Guidelines

Vitamin K administration is not recommended for correcting INR in patients with cirrhosis, as it does not improve INR in these patients, according to the most recent evidence 1. The use of vitamin K to correct prolongations in INR has been part of clinical practice for a long time in patients with chronic liver disease, but this practice is not supported by any evidence 1. Several studies have shown that vitamin K, especially when administered orally or subcutaneously, does not improve the INR 1.

Key Points to Consider

• The administration of vitamin K does not address the complex hemostatic changes in cirrhosis, which include both pro- and anti-coagulant alterations 1.
• Fresh frozen plasma or prothrombin complex concentrates are more effective for urgent INR correction before invasive procedures, though their benefit remains controversial in this population 1.
• The response to vitamin K can help differentiate between coagulopathy due to vitamin K deficiency versus liver dysfunction - minimal improvement suggests liver dysfunction as the primary cause 1.

Clinical Implications

• In patients with cirrhosis, the elevated INR primarily results from decreased synthesis of coagulation factors by the damaged liver rather than vitamin K deficiency 1.
• If vitamin K administration is deemed necessary, phytonadione (vitamin K1) can be given at doses of 5-10 mg subcutaneously or slowly intravenously daily for 3 days, but significant INR improvement is unlikely in most cirrhotic patients 1.
• Oral administration (5-10 mg) is also an option but may have reduced absorption in patients with cholestatic liver disease 1.

From the FDA Drug Label

Repeated large doses of phytonadione tablets are not warranted in liver disease if the response to initial use of the vitamin is unsatisfactory. The recommended dose to correct excessively prolonged prothrombin times caused by oral anticoagulant therapy is, 2. 5 mg to 10 mg or up to 25 mg initially. Evaluate INR after 6 to 8 hours, and repeat dose if INR remains prolonged.

The use of vitamin K to correct INR in patients with cirrhosis should be approached with caution. The initial dose of phytonadione is 2.5 mg to 10 mg or up to 25 mg, and the INR should be evaluated after 6 to 8 hours. If the INR remains prolonged, the dose can be repeated. However, repeated large doses are not warranted in liver disease if the response to the initial dose is unsatisfactory 2, 2.

• Key considerations:
  • Initial dose: 2.5 mg to 10 mg or up to 25 mg
  • Evaluate INR after 6 to 8 hours
  • Repeat dose if INR remains prolonged
  • Avoid repeated large doses in liver disease if initial response is unsatisfactory

From the Research

Correction of INR with Vitamin K in Cirrhosis

• The effectiveness of vitamin K in correcting cirrhosis-associated coagulopathy has been evaluated in several studies 3, 4, 5.
• A retrospective study of cirrhotic patients found that the use of intravenous vitamin K to correct coagulopathy may not be beneficial, with only 16.7% of patients meeting the primary effectiveness endpoint 3.
• Another study found that the administration of vitamin K for INR correction in critically ill patients with coagulopathy secondary to liver disease was not associated with a lower odds of new bleeding events 4.
• A retrospective investigation of patients with cirrhosis found that vitamin K administration did not affect INR changes or bleeding events 5.

Alternative Treatments

• Fresh frozen plasma (FFP) transfusion has been explored as an alternative treatment for coagulopathy in patients with cirrhosis 6, 7.
• A study found that FFP transfusion enhanced thrombin generation and ameliorated conventional coagulation tests to normal values in a limited number of patients, but also worsened them in a third of cases 6.
• Another study found that FFP infusions using the number of units commonly employed in clinical practice infrequently correct the coagulopathy of patients with chronic liver disease, with only 12.5% of patients achieving correction 7.

Efficacy of Vitamin K

• The efficacy of vitamin K in lowering an elevated INR in the setting of cirrhosis is not well established 5.
• A study found that delta of INR reduction was observed with a median of 0.63 when the first dose of vitamin K is given, but subsequent doses did not result in significant INR reduction 4.
• Another study found that vitamin K administration did not have a significant impact on INR changes or bleeding events in patients with cirrhosis 5.